Extracellular vesicle production: A bidirectional effect in the interplay between host and Candida fungi

Abstract

Candida fungi exploit various virulence strategies to invade the human host, while host cells employ diverse mechanisms to maintain homeostasis and respond to infection. Extracellular vesicles (EVs) are integral components of the multifaceted landscape of host-pathogen interactions, with their abundant production by all contributors involved in these complex and dynamic relations. Herein, we present the current state of knowledge regarding the host response by releasing EVs in reaction to Candida, as well as the influence of fungal EVs on the functionality of the confronted host cells. Fungal vesicles contribute to enhanced adhesion of pathogens to human cells as evidenced for C. auris, and may modulate the production of several cytokines, including IL-6, IL-8, IL-10, IL-12p40, TGF-β and TNF-α, thereby exerting pro-infective and pro-inflammatory effects, as described for C. albicans and other Candida species. Whereas the biosynthesis of EVs by host cells can dynamically modulate the proliferation and viability of fungal cells and affect the candidacidal functionality of other effector cells. The reciprocal influence of EVs from host cells and Candida pathogens is a key focus, explaining their significant role in cell signaling and interkingdom communication.

Keywords: Candida; Epithelium; Extracellular vesicles; Fungi; Host response; Inflammation; Macrophages.

Graphical abstract

Fig. 1

The schematic representation of the interactions and effects of EVs produced by the host (referred to as host EVs, hEVs) and by fungi of the genus Candida (referred to as fungal EVs, fEVs) documented to date. These influences are exerted on both fungal cells and host epithelial and immune cells, also taking into consideration the challenge of modulating the interaction milieu subsequent to the process of the initiation of the immune system activation and the further development of inflammation. The figure was created in part using Servier Medical Art, provided by Servier, and licensed under a Creative Commons Attribution 3.0 Unported license.